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Xia MC , Qi QA , Jin Y , Wiest DL , August A , Xiong N
Differential Roles of IL-2-Inducible T Cell Kinase-Mediated TCR Signals in Tissue-Specific Localization and Maintenance of Skin Intraepithelial T Cells
Journal of Immunology. 2010 Jun;184(12) :6807-6814
PMID: ISI:000278516700028    PMCID: PMC2941197   
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Tissue-specific innate-like gamma delta T cells are important components of the immune system critical for the first line of defense, but mechanisms underlying their tissue-specific development are poorly understood. Our study with prototypical skin-specific intraepithelial gamma delta T lymphocytes ( sIELs) found that among different thymic gamma delta T cell subsets fetal thymic precursors of sIELs specifically acquire a unique skin-homing property after positive selection, suggesting an important role of the TCR selection signaling in "programming" them for tissue-specific development. In this study, we identified IL-2-inducible T cell kinase (ITK) as a critical signal molecule regulating the acquirement of the skin-homing property by the fetal thymic sIEL precursors. In ITK knockout mice, the sIEL precursors could not undergo positive selection-associated upregulation of thymus-exiting and skin-homing molecules sphingosine-1-phosphate receptor 1 and CCR10 and accumulated in the thymus. However, the survival and expansion of sIELs in the skin did not require ITK-transduced TCR signaling, whereas its persistent activation impaired sIEL development by inducing apoptosis. These findings provide insights into molecular mechanisms underlying differential requirements of TCR signaling in peripheral localization and maintenance of the tissue-specific T cells. The Journal of Immunology, 2010, 184: 6807-6814.
Xia, Mingcan Qi, Qian Jin, Yan Wiest, David L. August, Avery Xiong, Na National Institutes of Health ; Pennsylvania Department of Health This work was supported by grants from the National Institutes of Health ( to N.X) and in part by a grant from the Pennsylvania Department of Health using Tobacco Settlement Funds ( to N.X.). 63 Amer assoc immunologists; 9650 rockville pike, bethesda, md 20814 usa 607pb